Unlocking Nature's Pharmacy
How an Indonesian Herbal Remedy Fights Both COVID-19 and Heart Disease
A computational journey reveals the molecular mechanisms behind traditional medicine
Introduction
In the midst of the COVID-19 pandemic, as hospitals overflowed and uncertainty prevailed, many Indonesians turned to a traditional solution: Empon-empon, a herbal formulation that has been part of Indonesian culture for generations 1 9 .
This blend of medicinal plants, typically including turmeric, ginger, galangal, and other natural ingredients, became a go-to remedy for those seeking to bolster their immune defenses. But beyond traditional wisdom, could there be scientific merit to these claims? Recently, a team of researchers embarked on a computational journey to unravel the molecular mysteries behind Empon-empon's therapeutic potential. Their fascinating discovery? The same herbal preparation that many used to combat COVID-19 may also protect against atherosclerosis, the dangerous artery hardening that underlies heart attacks and strokes 1 .
This convergence is particularly significant because scientists have observed an alarming connection between COVID-19 and cardiovascular complications. The same inflammatory processes that make COVID-19 severe also drive the progression of atherosclerosis 1 .
COVID-19
A respiratory illness caused by SARS-CoV-2 that can lead to severe inflammation and cytokine storms.
Atherosclerosis
A cardiovascular disease characterized by plaque buildup in arteries, driven by chronic inflammation.
The Science of Herbal Medicine: From Tradition to Validation
The Connection Between COVID-19 and Atherosclerosis
At first glance, a respiratory illness and artery disease might seem unrelated, but they share common biological pathways. Both conditions involve excessive inflammation—an overzealous immune response that can damage the body's own tissues. In severe COVID-19 cases, this manifests as a "cytokine storm," where the immune system becomes dangerously overactive 3 . Similarly, atherosclerosis is now recognized as fundamentally an inflammatory disorder of the arteries, where chronic inflammation promotes the buildup of fatty plaques in blood vessel walls 5 6 .
When these plaques become unstable and rupture, they can trigger blood clots that lead to heart attacks or strokes. Researchers have found that SARS-CoV-2 infection can worsen this underlying cardiovascular vulnerability, creating a double threat to patient health 1 . This intersection between infectious and cardiovascular diseases prompted scientists to investigate whether Empon-empon's reported benefits against COVID-19 might extend to protecting blood vessels as well.
The Bioinformatics Revolution in Natural Product Research
Studying complex herbal mixtures like Empon-empon presents significant challenges. With dozens of active compounds interacting with hundreds of molecular targets in the human body, traditional laboratory methods alone would be prohibitively time-consuming and expensive. This is where bioinformatics—the application of computational tools to biological data—has revolutionized the field 1 .
By combining network pharmacology (which maps complex compound-target interactions) with molecular docking (which simulates how compounds bind to proteins), researchers can now virtually screen natural products for therapeutic potential before ever setting foot in a wet lab 1 . This approach respects the holistic nature of traditional medicine while subjecting it to rigorous scientific scrutiny.
Key Insight
Bioinformatics allows researchers to study complex herbal mixtures in their entirety, respecting the traditional holistic approach while providing scientific validation.
Empon-empon Ingredients
Turmeric
Curcumin
Ginger
Gingerol
Galangal
Galangin
Temulawak
CurcuminoidsThe Bioinformatics Expedition: A Step-by-Step Journey
Step 1: Identifying the Active Compounds
The research team began by compiling a comprehensive list of Empon-empon's chemical constituents from natural product databases. Through rigorous screening, they narrowed the field to 18 primary bioactive compounds that met pharmaceutical criteria for oral bioavailability (how well a substance is absorbed when taken orally) and drug-likeness (how suitable a molecule is as a drug candidate) 1 2 .
Step 2: Mapping the Targets
Next, the researchers identified the specific human proteins that these compounds interact with—their "molecular targets." Simultaneously, they compiled lists of proteins known to be involved in both COVID-19 and atherosclerosis pathogenesis. The intersection of these datasets revealed the key protein targets through which Empon-empon might exert its dual therapeutic effects 1 .
Step 3: Building Networks and Pathways
Using protein-protein interaction databases, the team constructed a network map showing how Empon-empon's protein targets communicate with each other and with disease-related proteins. They then analyzed these networks to identify the biological pathways most significantly affected by the herbal preparation 1 .
Step 4: Molecular Docking
In the final phase, researchers performed virtual molecular docking experiments to simulate how Empon-empon's most promising compounds physically interact with their key protein targets. The strength of these molecular interactions was quantified as binding affinity—with stronger (more negative) values indicating tighter and more potentially effective binding 1 .
Research Methodology Overview
Remarkable Findings: Nature's Sophisticated Pharmacology
Key Compounds and Their Targets
The bioinformatics analysis revealed that Empon-empon contains multiple compounds with significant potential against both COVID-19 and atherosclerosis.
| Compound | Natural Source | Primary Molecular Targets | Therapeutic Potential |
|---|---|---|---|
| Catechin | Turmeric, Green Tea | EP300 | Antioxidant, anti-inflammatory |
| Quercetin | Various fruits, vegetables | EP300 | Antiviral, anti-inflammatory |
| Licarin B | Nutmeg | HSP90AA1, RELA | Anti-inflammatory |
| Delphinidin | Blue-red fruits | HSP90AA1, SRC | Antioxidant, cardiovascular protection |
| Epicatechin | Turmeric, Cacao | SRC | Anti-inflammatory, endothelial protection |
| Galangin | Galangal | ESR1 | Antioxidant, antiviral |
| Ellagic acid | Various plants | ESR1 | Antioxidant, anti-atherosclerotic |
| Guaiacin | Ginger family | RELA | Anti-inflammatory |
The Central Players: Five Key Proteins in Both Diseases
The research identified five proteins that appear to be central to both COVID-19 and atherosclerosis, and which are significantly targeted by Empon-empon compounds.
E1A Binding Protein P300
Regulates inflammatory gene expression
Strongest-binding Compounds: Catechin, Quercetin
Heat Shock Protein 90 Alpha Family Class A Member 1
Stabilizes proteins involved in inflammation and viral replication
Strongest-binding Compounds: Licarin B, Delphinidin
SRC Proto-Oncogene
Signaling in inflammation and plaque formation
Strongest-binding Compounds: Epicatechin, Delphinidin
Estrogen Receptor 1
Modulates vascular inflammation and immune response
Strongest-binding Compounds: Galangin, Ellagic acid
Molecular Docking Results
The virtual binding experiments yielded impressive results, with many natural compounds showing strong binding affinities to their protein targets.
The Scientist's Toolkit: Key Research Reagents and Methods
This groundbreaking research was made possible by sophisticated computational tools and databases.
KNApSAcK
Type: Database
Function: Natural compound repository
Application: Identifying Empon-empon's active compounds
GeneCards
Type: Database
Function: Gene-protein database
Application: Mapping compound and disease targets
TCMSP
Type: Database
Function: Traditional Chinese Medicine systems pharmacology
Application: Screening bioactive compounds
STRING
Type: Database
Function: Protein-protein interactions
Application: Building interaction networks
Cytoscape
Type: Software
Function: Network visualization
Application: Visualizing compound-target-disease networks
AutoDock Vina
Type: Software
Function: Molecular docking
Application: Simulating compound-protein binding
Implications and Future Directions: Bridging Traditional Wisdom and Modern Medicine
A Multi-Pronged Therapeutic Approach
The most remarkable finding of this research is how Empon-empon's diverse compounds target multiple disease mechanisms simultaneously—a distinct advantage over single-target pharmaceutical approaches. While statins (the primary conventional treatment for atherosclerosis) mainly lower cholesterol, and antivirals target specific viral components, Empon-empon appears to address inflammation, immune dysregulation, and vascular protection concurrently 1 6 .
The network analysis revealed that Empon-empon's compounds influence several key pathways involved in both diseases, including the PI3K-Akt signaling pathway (important for cell survival and inflammation), lipid and atherosclerosis pathways, and specific coronavirus disease-related pathways 1 . This multi-target action aligns perfectly with the holistic approach of traditional medicine while offering mechanistic explanations for its purported benefits.
Cultural Significance and Modern Relevance
The validation of Empon-empon through modern scientific methods represents an important reconciliation of traditional knowledge with contemporary medicine. For generations, Indonesian households have prepared and consumed these herbal mixtures based on empirical evidence passed down through families. During the pandemic, this tradition saw a significant resurgence—a survey conducted across Indonesia's 33 provinces found that 62.7% of respondents used herbal medicine during the COVID-19 crisis 3 .
The same survey revealed that herbal medicine use was significantly influenced by age and occupation, with students and residents of Java Island representing the largest consumer groups. Popular ingredients included ginger, turmeric, and lime—all components typically found in Empon-empon preparations 3 . This widespread use underscores the cultural importance of traditional remedies and the need for scientific validation to ensure safety and efficacy.
Herbal Medicine Usage During COVID-19 in Indonesia
Future Research and Clinical Applications
While the bioinformatics findings are promising, the researchers emphasize that these computational results require validation through laboratory experiments and clinical trials. The study provides a strong foundation for future research by prioritizing the most promising compounds and revealing their likely mechanisms of action 1 .
Next steps would include testing these compounds in cell culture and animal models of COVID-19 and atherosclerosis, followed by carefully designed human clinical trials. The ultimate goal would be to develop standardized Empon-empon-based formulations that could serve as complementary approaches to conventional treatments, potentially reducing reliance on pharmaceuticals with significant side effects 5 6 .
Conclusion
The bioinformatics expedition into Empon-empon represents a perfect marriage between traditional wisdom and cutting-edge science. By demonstrating through computational methods how this traditional Indonesian formulation can target shared biological mechanisms of COVID-19 and atherosclerosis, researchers have opened exciting new avenues for drug development while validating centuries of traditional use.
This article is based on the study "DECODING THE THERAPEUTIC POTENTIAL OF EMPON-EMPON: A BIOINFORMATICS EXPEDITION UNRAVELING MECHANISMS AGAINST COVID-19 AND ATHEROSCLEROSIS" published in the International Journal of Applied Pharmaceutics (2024) and supplementary research on herbal medicine usage during the COVID-19 pandemic in Indonesia.